Dap-modified LL-37 analogs gain 5.7-fold protease stability, lose antibacterial activity

The wire

1. 01Researchers replaced arginine, lysine or isoleucine residues in LL-37 with 2,3-diaminopropionic acid bearing oxa-acid spacers; the arginine Dap(GO1) analog showed 5.7-fold greater stability against proteinase 3.
2. 02LL-37's therapeutic use has been limited by rapid proteolysis and PAD-mediated citrullination; the authors present a modular route to tune cathelicidin function toward immunomodulation.
3. 03All six analogs lost direct antibacterial activity and were tested only in vitro at 1-10 micromolar; the intracellular mechanism, including TLR4/FPR2 engagement, was not assayed.

From the source

Building Blocks of 2,3-Diaminopropionic Acid Functionalized with an Oxa-Acid Spacer Shift the Functional Profile of Human Cathelicidin LL-37: Enhanced Enzymatic Stability and Selective Suppression of Neutrophil Degranulation

Pharmaceuticals (Basel, Switzerland) · 2026 Jul 24 · Rejmak W, Bury K, Bauer M et al.